Drug Discovery@nature.com 11 October 2013

TABLE OF CONTENTS 11 October 2013 News Analysis Research Highlights Research & Reviews Careers Nature Reviews Drug Discovery is on Twitter Advertisement SciBX: Science-Business eXchange Collection on Antibiotic Resistance This special Collection from SciBX: Science-Business eXchange provides an overview of the state of affairs on antibiotic resistance from the scientific, business and regulatory perspectives.  Click here to access the Collection for free! Produced with support from: Cempra Inc., Cubist Pharmaceuticals Inc., Durata Therapeutics Inc., Polyphor Ltd.   News Top First IL-6–blocking drug nears approval for rare blood disorder doi:10.1038/nm1013-1193 Last month, Janssen R&D submitted applications to drug regulators for the antibody drug siltuximab for the treatment of multicentric Castleman's disease. If approved, siltuximab would be the first drug that directly targets IL-6 to make it to market. Full Text Caution urged over the FDA's new breakthrough designation doi:10.1038/nm1013-1196a The FDA established the 'breakthrough therapy' designation in 2012, offering expedited review and approval pathways for drugs for serious diseases. Now, some researchers are raising concerns over whether patient safety is being overlooked in the pursuit of speeding drugs to market. Full Text An audience with…Daniel Hayes doi:10.1038/nrd4137 Daniel Hayes discusses how to break the vicious cycle that is keeping biomarkers down. Full Text Finding the right chemistry doi:10.1038/nm1013-1200 Discovering the right compound that can treat an infection such as HIV is only the first piece of the drug development puzzle. The next challenge is to make the manufacturing process more efficient - and thereby cheaper. Killugudi Jayaraman meets with the 'process chemistry' experts honing these reactions to bring down the cost of antiretrovirals. Full Text Analysis Top Escaping abiraterone doi:10.1038/scibx.2013.1049 Although a lot is known about how castration-resistant prostate cancers become refractory to second-generation androgen receptor antagonists, the mechanism behind resistance to CYP17 inhibitors remains a mystery. An alternative androgen synthesis pathway identified by a team from the Cleveland Clinic may change the game. Full Text Pharmaceutical forecasting: throwing darts? doi:10.1038/nrd4127 Forecasting of the future commercial value of drugs is a crucial activity that affects many decisions by pharmaceutical companies. However, this analysis indicates that many forecasts are wrong, often substantially. Full Text Research Highlights Top Anticancer drugs: Stapled peptide reactivates p53 doi:10.1038/nrd4133 The stapled α-helical peptide ATSP-7041 - which is a specific dual inhibitor of MDM2 and MDMX - effectively induces p53-dependent apoptosis and inhibits cell proliferation in mouse models of human tumours. Full Text Biotechnology: Rice-derived rotavirus antibody shows promise doi:10.1038/nrd4131 Researchers have genetically engineered rice to produce high yields of a rotavirus-specific antibody fragment in the seeds. This antibody was effective in treating and preventing rotavirus-induced gastrointestinal symptoms in mice. Full Text Neurodegenerative diseases: New kinase targets for Alzheimer's disease doi:10.1038/nrd4132 Two recent studies show that inhibiting kinases involved in the regulation of amyloid precursor protein processing or protein synthesis by eukaryotic translation initiation factor 2α attenuates disease progression in mice. Full Text Research & Reviews Top Considerations for the successful co-development of targeted cancer therapies and companion diagnostics doi:10.1038/nrd4101 The authors discuss issues relating to the co-development of targeted cancer therapies and companion diagnostics that were not covered in depth in the draft guidance released by the US FDA in 2011. They also propose potential strategies that will be useful to mitigate challenges and to help guide the future co-development of drugs and diagnostics. Full Text Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology doi:10.1038/nrc3580 Anaplastic lymphoma kinase (ALK) is commonly altered - through mutation, overexpression or translocation - in many types of cancer, but the role of ALK signalling in mammalian cells and tumours remains enigmatic. What can we learn from model systems? And what progress has been made in targeting this receptor tyrosine kinase? Full Text p11 and its role in depression and therapeutic responses to antidepressants doi:10.1038/nrn3564 Recent studies have shown that the protein p11 (also known as S100A10) has an important role in depression-like behaviour and antidepressant actions. Greengard and colleagues discuss the molecular and cellular mechanisms that may underlie this role. Full Text Macrophages in atherosclerosis: a dynamic balance doi:10.1038/nri3520 In this Review, the authors provide a comprehensive overview of the role of macrophage dynamics in determining the initiation, progression and regression of atherosclerotic inflammation. Understanding the factors that determine the inflammatory state of the plaque may help to identify potential therapeutic targets for plaque regression. Full Text Drug Discovery JOBS of the week Postdoctoral fellow in human liver tissue engineering for drug and toxicology studies. Duke University Biomedical Engineering Department OCE Postdoctoral Fellowship Ocular Drug Delivery CSIRO (Commonwealth Scientific & Industrial Research Organisation) Postdoc Fellow� Drug / siRNA delivery nanoparticle-Polymer Chemistry�Molecular Biology University of Hawaii at Hilo, The Daniel K. Inouye College of Pharmacy PhD fellowship with focus on genetic interactions in response to drug treatment Technical University of Denmark (DTU) Asst / Assoc / Full Professor - Medicinal Chemistry / Drug Discovery Saint Louis University School of Medicine More Science jobs from Drug Discovery EVENT The Biology of Aging: Novel Drug Targets for Neurodegenerative Disease 09.05.14 New York, US More science events from Careers Top Career snapshots archive Career snapshots feature people associated with drug discovery and drug development, with the aim of providing expert insights and advice on a wide range of positions and career paths in this field. Full Text Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.